Please use this identifier to cite or link to this item: https://doi.org/10.1242/bio.012005
DC FieldValue
dc.titleSonic hedgehog functions upstream of disrupted-in-schizophrenia 1 (disc1): Implications for mental illness
dc.contributor.authorBoyd, P.J
dc.contributor.authorCunliffe, V.T
dc.contributor.authorRoy, S
dc.contributor.authorWood, J.D
dc.date.accessioned2020-10-26T08:31:57Z
dc.date.available2020-10-26T08:31:57Z
dc.date.issued2015
dc.identifier.citationBoyd, P.J, Cunliffe, V.T, Roy, S, Wood, J.D (2015). Sonic hedgehog functions upstream of disrupted-in-schizophrenia 1 (disc1): Implications for mental illness. Biology Open 4 (10) : 1336-1343. ScholarBank@NUS Repository. https://doi.org/10.1242/bio.012005
dc.identifier.issn20466390
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/180356
dc.description.abstractDISRUPTED-IN-SCHIZOPHRENIA (DISC1) has been one of the most intensively studied genetic risk factors for mental illness since it was discovered through positional mapping of a translocation breakpoint in a large Scottish family where a balanced chromosomal translocation was found to segregate with schizophrenia and affective disorders. While the evidence for it being central to disease pathogenesis in the original Scottish family is compelling, recent genome-wide association studies have not found evidence for common variants at the DISC1 locus being associated with schizophrenia in the wider population. It may therefore be the case that DISC1 provides an indication of biological pathways that are central to mental health issues and functional studies have shown that it functions in multiple signalling pathways. However, there is little information regarding factors that function upstream of DISC1 to regulate its expression and function. We herein demonstrate that Sonic hedgehog (Shh) signalling promotes expression of disc1 in the zebrafish brain. Expression of disc1 is lost in smoothened mutants that have a complete loss of Shh signal transduction, and elevated in patched mutants which have constitutive activation of Shh signalling. We previously demonstrated that disc1 knockdown has a dramatic effect on the specification of oligodendrocyte precursor cells (OPC) in the hindbrain and Shh signalling is known to be essential for the specification of these cells. We show that disc1 is prominently expressed in olig2-positive midline progenitor cells that are absent in smo mutants, while cyclopamine treatment blocks disc1 expression in these cells and mimics the effect of disc1 knock down on OPC specification. Various features of a number of psychiatric conditions could potentially arise through aberrant Hedgehog signalling. We therefore suggest that altered Shh signalling may be an important neurodevelopmental factor in the pathobiology of mental illness. © 2015. Published by The Company of Biologists Ltd.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectcyclopamine
dc.subjectdisrupted in schizophrenia 1 protein
dc.subjectmutant protein
dc.subjectprotein Patched 1
dc.subjectprotein Patched 2
dc.subjectsonic hedgehog protein
dc.subjectanimal cell
dc.subjectanimal embryo
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectaxon
dc.subjectcell labeling
dc.subjectcontrolled study
dc.subjectembryo
dc.subjectimmunofluorescence test
dc.subjectin situ hybridization
dc.subjectmental disease
dc.subjectmolecular pathology
dc.subjectmotoneuron
dc.subjectneuromere
dc.subjectnonhuman
dc.subjectoligodendrocyte precursor cell
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectquantitative analysis
dc.subjectreverse transcription polymerase chain reaction
dc.subjectrhombencephalon
dc.subjectsignal transduction
dc.subjectzebra fish
dc.typeArticle
dc.contributor.departmentDEPT OF BIOLOGICAL SCIENCES
dc.description.doi10.1242/bio.012005
dc.description.sourcetitleBiology Open
dc.description.volume4
dc.description.issue10
dc.description.page1336-1343
dc.published.statePublished
Appears in Collections:Elements
Staff Publications

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1242_bio_012005.pdf724.63 kBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons